Reference : Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cance...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/54549

Title :	Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis
Language :	English
Author, co-author :	Kiweler, Nicole [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Delbrouck, Catherine [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Pozdeev, Vitaly [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Neises, Laura [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Soriano-Bague, Leticia [Faculty of Science, Technology and Medicine, University of Luxembourg, 2 avenue de Université, Esch-sur-Alzette, Luxembourg.]
	Eiden, Kim [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Xian, Feng [Proteomics of cellular signaling, Department of Infection and Immunity, Luxembourg Institute of Health,1a Rue Thomas Edison, Strassen, Luxembourg]
	Benzarti, Mohaned [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Haase, Lara [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Koncina, Eric [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Schmoetten, Maryse [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Jaeger, Christian [Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg]
	Zaeem Noman, Muhammad [Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Vazquez, Alexei [Institute of Cancer Sciences, University of Glasgow, Glasgow, UK]
	Janji, Bassam [Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Dittmar, Gunnar [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > >]
	Brenner, Dirk [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics >]
	Letellier, Elisabeth [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Meiser, Johannes [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
Publication date :	2022
Journal title :	Nature Communications
Publisher :	Nature Publishing Group
Peer reviewed :	Yes
Audience :	International
e-ISSN :	2041-1723
City :	London
Country :	United Kingdom
Keywords :	[en] Mitochondria ; one-carbon (1C) metabolism ; cell migration cell migration
Abstract :	[en] Metastasis is the most common cause of death in cancer patients. Canonical drugs target mainly the proliferative capacity of cancer cells, which leaves slow-proliferating, persistent cancer cells unaffected. Metabolic determinants that contribute to growth-independent functions are still poorly understood. Here we show that antifolate treatment results in an uncoupled and autarkic mitochondrial one-carbon (1C) metabolism during cytosolic 1C metabolism impairment. Interestingly, antifolate dependent growth-arrest does not correlate with decreased migration capacity. Therefore, using methotrexate as a tool compound allows us to disentangle proliferation and migration to profile the metabolic phenotype of migrating cells. We observe that increased serine de novo synthesis (SSP) supports mitochondrial serine catabolism and inhibition of SSP using the competitive PHGDH-inhibitor BI-4916 reduces cancer cell migration. Furthermore, we show that sole inhibition of mitochondrial serine catabolism does not affect primary breast tumor growth but strongly inhibits pulmonary metastasis. We conclude that mitochondrial 1C metabolism, despite being dispensable for proliferative capacities, confers an advantage to cancer cells by supporting their motility potential.
Target :	Researchers
Permalink :	http://hdl.handle.net/10993/54549
DOI :	10.1038/s41467-022-30363-y

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